89 research outputs found
Reduced expression of the psychiatric risk gene DLG2 (PSD93) impairs hippocampal synaptic integration and plasticity
Growth-in-place deployment of in-plane silicon nanowires
International audienceUp-scaling silicon nanowire (SiNW)-based functionalities requires a reliable strategy to precisely position and integrate individual nanowires. We here propose an all-in-situ approach to fabricate self-positioned/aligned SiNW, via an in-plane solid-liquid-solid growth mode. Prototype field effect transistors, fabricated out of in-plane SiNWs using a simple bottom-gate configuration, demonstrate a hole mobility of 228 cm2/V s and on/off ratio >103. Further insight into the intrinsic doping and structural properties of these structures was obtained by laser-assisted 3 dimensional atom probe tomography and high resolution transmission electron microscopy characterizations. The results could provide a solid basis to deploy the SiNW functionalities in a cost-effective way
Effects of a multimedia campaign on HIV self-testing and PrEP outcomes among young people in South Africa: a mixed-methods impact evaluation of 'MTV Shuga Down South'.
INTRODUCTION: Innovative HIV technologies can help to reduce HIV incidence, yet uptake of such tools is relatively low among young people. To create awareness and demand among adolescents and young adults, a new campaign of the pan-African MTV Shuga series ('Down South 2'; DS2), featured storylines and messages about HIV self-testing (HIVST) and pre-exposure prophylaxis (PrEP) through television, radio and accompanying multimedia activities in 2019-2020. METHODS: We conducted a mixed-methods evaluation of the new MTV Shuga series among 15-24 years old in Eastern Cape, South Africa, in 2020. Quantitative and qualitative methods were used to investigate complementary evaluations questions, namely, whether and how the DS2 campaign works. A web-based survey, promoted via social media platforms of schools, universities and communities, assessed exposure to MTV Shuga and knowledge of HIV status; secondary outcomes included awareness and uptake of HIVST and PrEP. We used multivariable logistic regression to estimate associations between exposure to DS2 and each outcome, adjusting for sociodemographic factors, media assets and exposure to other media campaigns. An embedded qualitative evaluation explored mechanisms of DS2's impact through deductive and inductive thematic analysis of in-depth individual and group interviews. RESULTS: Among 3431 online survey participants, 43% had engaged with MTV Shuga and 24% with DS2 specifically. Knowledge of HIV status was higher among those exposed to DS2 (71%) vs those who were not (39%; adjusted OR=2.26 (95% CI 1.78 to 2.87)). Exposure was also associated with increased awareness of HIVST (60% vs 28%; aOR=1.99 (1.61 to 2.47)) and use of HIVST (29% vs 10%; aOR=2.49 (1.95 to 3.19)). One-third of respondents were aware of PrEP, with higher proportions among those exposed versus non-exposed to DS2 (52% vs 27%; aOR=1.90 (1.53 to 2.35)). Qualitative insights identified mechanisms by which DS2 increased awareness, confidence and motivation to use HIVST and PrEP, but had less influence on service access. CONCLUSIONS: We found evidence consistent with a positive causal impact of the MTV Shuga DS2 campaign on HIV prevention outcomes among young people in a high-prevalence setting. As diverse testing and PrEP technologies become accessible, an immersive edutainment campaign can help to expand HIV prevention choices and close age and gender gaps in HIV testing and prevention goals
Estimates of Pandemic Influenza Vaccine Effectiveness in Europe, 2009–2010: Results of Influenza Monitoring Vaccine Effectiveness in Europe (I-MOVE) Multicentre Case-Control Study
Results from a European multicentre case-control study reported by Marta Valenciano and colleagues suggest good protection by the pandemic monovalent H1N1 vaccine against pH1N1 and no effect of the 2009–2010 seasonal influenza vaccine on H1N1
Reduced expression of the psychiatric risk gene DLG2 (PSD93) impairs hippocampal synaptic integration and plasticity
Copy number variants indicating loss of function in the DLG2 gene have been associated with markedly increased risk for schizophrenia, autism spectrum disorder, and intellectual disability. DLG2 encodes the postsynaptic scaffolding protein DLG2 (PSD93) that interacts with NMDA receptors, potassium channels, and cytoskeletal regulators but the net impact of these interactions on synaptic plasticity, likely underpinning cognitive impairments associated with these conditions, remains unclear. Here, hippocampal CA1 neuronal excitability and synaptic function were investigated in a novel clinically relevant heterozygous Dlg2+/− rat model using ex vivo patch-clamp electrophysiology, pharmacology, and computational modelling. Dlg2+/− rats had reduced supra-linear dendritic integration of synaptic inputs resulting in impaired associative long-term potentiation. This impairment was not caused by a change in synaptic input since NMDA receptor-mediated synaptic currents were, conversely, increased and AMPA receptor-mediated currents were unaffected. Instead, the impairment in associative long-term potentiation resulted from an increase in potassium channel function leading to a decrease in input resistance, which reduced supra-linear dendritic integration. Enhancement of dendritic excitability by blockade of potassium channels or activation of muscarinic M1 receptors with selective allosteric agonist 77-LH-28-1 reduced the threshold for dendritic integration and 77-LH-28-1 rescued the associative long-term potentiation impairment in the Dlg2+/− rats. These findings demonstrate a biological phenotype that can be reversed by compound classes used clinically, such as muscarinic M1 receptor agonists, and is therefore a potential target for therapeutic intervention
I-MOVE Multi-Centre Case Control Study 2010-11: Overall and Stratified Estimates of Influenza Vaccine Effectiveness in Europe
BACKGROUND: In the third season of I-MOVE (Influenza Monitoring Vaccine Effectiveness in Europe), we undertook a multicentre case-control study based on sentinel practitioner surveillance networks in eight European Union (EU) member states to estimate 2010/11 influenza vaccine effectiveness (VE) against medically-attended influenza-like illness (ILI) laboratory-confirmed as influenza. METHODS: Using systematic sampling, practitioners swabbed ILI/ARI patients within seven days of symptom onset. We compared influenza-positive to influenza laboratory-negative patients among those meeting the EU ILI case definition. A valid vaccination corresponded to > 14 days between receiving a dose of vaccine and symptom onset. We used multiple imputation with chained equations to estimate missing values. Using logistic regression with study as fixed effect we calculated influenza VE adjusting for potential confounders. We estimated influenza VE overall, by influenza type, age group and among the target group for vaccination. RESULTS: We included 2019 cases and 2391 controls in the analysis. Adjusted VE was 52% (95% CI 30-67) overall (N = 4410), 55% (95% CI 29-72) against A(H1N1) and 50% (95% CI 14-71) against influenza B. Adjusted VE against all influenza subtypes was 66% (95% CI 15-86), 41% (95% CI -3-66) and 60% (95% CI 17-81) among those aged 0-14, 15-59 and ≥60 respectively. Among target groups for vaccination (N = 1004), VE was 56% (95% CI 34-71) overall, 59% (95% CI 32-75) against A(H1N1) and 63% (95% CI 31-81) against influenza B. CONCLUSIONS: Results suggest moderate protection from 2010-11 trivalent influenza vaccines against medically-attended ILI laboratory-confirmed as influenza across Europe. Adjusted and stratified influenza VE estimates are possible with the large sample size of this multi-centre case-control. I-MOVE shows how a network can provide precise summary VE measures across Europe
Micrometeoroid Events in LISA Pathfinder
The zodiacal dust complex, a population of dust and small particles that
pervades the Solar System, provides important insight into the formation and
dynamics of planets, comets, asteroids, and other bodies. Here we present a new
set of data obtained using a novel technique: direct measurements of momentum
transfer to a spacecraft from individual particle impacts. This technique is
made possible by the extreme precision of the instruments flown on the LISA
Pathfinder spacecraft, a technology demonstrator for a future space-based
gravitational wave observatory that operated near the first Sun-Earth Lagrange
point from early 2016 through Summer of 2017. Using a simple model of the
impacts and knowledge of the control system, we show that it is possible to
detect impacts and measure properties such as the transferred momentum (related
to the particle's mass and velocity), direction of travel, and location of
impact on the spacecraft. In this paper, we present the results of a systematic
search for impacts during 4348 hours of Pathfinder data. We report a total of
54 candidates with momenta ranging from 0.2 to
230. We furthermore make a comparison of these candidates
with models of micrometeoroid populations in the inner solar system including
those resulting from Jupiter-family comets, Oort-cloud comets, Hailey-type
comets, and Asteroids. We find that our measured population is consistent with
a population dominated by Jupiter-family comets with some evidence for a
smaller contribution from Hailey-type comets. This is in agreement with
consensus models of the zodiacal dust complex in the momentum range sampled by
LISA Pathfinder.Comment: 22 pages, 14 figures, accepted in Ap
Support for UNRWA's survival
The United Nations Relief and Works Agency for Palestine Refugees in the Near East (UNRWA) provides life-saving humanitarian aid for 5·4 million Palestine refugees now entering their eighth decade of statelessness and conflict. About a third of Palestine refugees still live in 58 recognised camps. UNRWA operates 702 schools and 144 health centres, some of which are affected by the ongoing humanitarian disasters in Syria and the Gaza Strip. It has dramatically reduced the prevalence of infectious diseases, mortality, and illiteracy. Its social services include rebuilding infrastructure and homes that have been destroyed by conflict and providing cash assistance and micro-finance loans for Palestinians whose rights are curtailed and who are denied the right of return to their homeland
Screening for HIV-Associated Tuberculosis and Rifampicin Resistance before Antiretroviral Therapy Using the Xpert MTB/RIF Assay: A Prospective Study
In a prospective study, Stephen Lawn and colleagues find that pre-ART screening with Xpert MTB/RIF increased tuberculosis case detection by 45% compared to smear microscopy in HIV-positive patients at high risk of TB risk. AE competing interests must also pull through to the proof. “The Academic Editor, Madhukar Pai, declares that he consults for the Bill & Melinda Gates Foundation (BMGF). The BMGF supported FIND which was involved in the development of the Xpert MTB/RIF assay. He also co-chairs the Stop TB Partnership's New Diagnostics Working Group that was involved in the WHO endorsement of the Xpert assay.” Linked: Scott pmed.1001061; Evans pmed.1001064; Dowdy pmed.100106
Gram-Negative Bacterial Sensors for Eukaryotic Signal Molecules
Ample evidence exists showing that eukaryotic signal molecules synthesized and released by the host can activate the virulence of opportunistic pathogens. The sensitivity of prokaryotes to host signal molecules requires the presence of bacterial sensors. These prokaryotic sensors, or receptors, have a double function: stereospecific recognition in a complex environment and transduction of the message in order to initiate bacterial physiological modifications. As messengers are generally unable to freely cross the bacterial membrane, they require either the presence of sensors anchored in the membrane or transporters allowing direct recognition inside the bacterial cytoplasm. Since the discovery of quorum sensing, it was established that the production of virulence factors by bacteria is tightly growth-phase regulated. It is now obvious that expression of bacterial virulence is also controlled by detection of the eukaryotic messengers released in the micro-environment as endocrine or neuro-endocrine modulators. In the presence of host physiological stress many eukaryotic factors are released and detected by Gram-negative bacteria which in return rapidly adapt their physiology. For instance, Pseudomonas aeruginosa can bind elements of the host immune system such as interferon-γ and dynorphin and then through quorum sensing circuitry enhance its virulence. Escherichia coli sensitivity to the neurohormones of the catecholamines family appears relayed by a recently identified bacterial adrenergic receptor. In the present review, we will describe the mechanisms by which various eukaryotic signal molecules produced by host may activate Gram-negative bacteria virulence. Particular attention will be paid to Pseudomonas, a genus whose representative species, P. aeruginosa, is a common opportunistic pathogen. The discussion will be particularly focused on the pivotal role played by these new types of pathogen sensors from the sensing to the transduction mechanism involved in virulence factors regulation. Finally, we will discuss the consequence of the impact of host signal molecules on commensally or opportunistic pathogens associated with different human tissue
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